Lu Lab

About The Lu Lab

The Lu Lab's research interests lie at the interface between chemistry and biology. Specific areas of current interests include a) computational design and engineering of functional metalloenzymes as environmentally benign catalysts in renewable energy generation and pharmaceuticals; b) Fundamental understanding of DNAzymes and their applications in environmental monitoring, medical diagnostics, gene editing and targeted drug delivery; and c) Employing principles from biology for directed assembly of nanomaterials with controlled morphologies and its applications in imaging and medicine.

Current projects of interests include a) computational design of artificial metalloenzymes employing machine learning methods for solar energy transfer, (bio)fuel cells, CO₂ reduction and nitrogen fixation; b) design of selective sensors and imaging agents for metal ions and metabolites to advance metallomics and metabolomics for medical diagnosis and imaging in neurodegenerative diseases and cancers; and c) developing novel gene-editing methods to improve sequence fidelity and gene target accessibility.

2023 Research

• Cooke DJ, Maier EY, King TL, Lin H, Hendrichs S, Lee S, Mafy NN, Scott KM, Lu Y, Que EL. Dual Nanoparticle Conjugates for Highly Sensitive and Versatile Sensing Using 19F Magnetic Resonance Imaging. Angew Chem Int Ed Engl. 2023 Nov 28:e202312322. Epub ahead of print. PMID: 38016929.

• Wang JX, Vilbert AC, Cui C, Mirts EN, Williams LH, Kim W, Jessie Zhang Y, Lu Y. Increasing Reduction Potentials of Type 1 Copper Center and Catalytic Efficiency of Small Laccase from Streptomyces coelicolor through Secondary Coordination Sphere Mutations. Angew Chem Int Ed Engl. 2023 Nov 5:e202314019. Epub ahead of print. PMID: 37926680.

• Liu Y, Harnden KA, Van Stappen C, Dikanov SA, Lu Y. A designed Copper Histidine-brace enzyme for oxidative depolymerization of polysaccharides as a model of lytic polysaccharide monooxygenase. Proc Natl Acad Sci U S A. 2023 Oct 24;120(43):e2308286120. Epub 2023 Oct 16. PMID: 37844252; PMCID: PMC10614608.

• Van Stappen C, Dai H, Jose A, Tian S, Solomon EI, Lu Y. Primary and Secondary Coordination Sphere Effects on the Structure and Function of S-Nitrosylating Azurin. J Am Chem Soc. 2023 Sep 20;145(37):20610-20623. Epub 2023 Sep 11. PMID: 37696009; PMCID: PMC10539042.

• McGuinness KN, Fehon N, Feehan R, Miller M, Mutter AC, Rybak LA, Nam J, AbuSalim JE, Atkinson JT, Heidari H, Losada N, Kim JD, Koder RL, Lu Y, Silberg JJ, Slusky JSG, Falkowski PG, Nanda V. The energetics and evolution of oxidoreductases in deep time. Proteins. 2023 Aug 19. Epub ahead of print. PMID: 37596815.

• Xiong M, Wu Y, Kong G, Lewis W, Yang Z, Zhang H, Xu L, Liu Y, Liu Q, Zhao X, Zhang XB, Lu Y. A Semisynthetic Bioluminescence Sensor for Ratiometric Imaging of Metal Ions In Vivo Using DNAzymes Conjugated to An Engineered Nano- Luciferase. Angew Chem Int Ed Engl. 2023 Aug 7:e202308086. Epub ahead of print. PMID: 37548922.

• Liu Y, Marshall NM, Yu SS, Kim W, Gao YG, Robinson H, Nilges MJ, Zhang Y, New SY, Lu Y. Structural Basis for the Effects of Phenylalanine on Tuning the Reduction Potential of Type 1 Copper in Azurin. Inorg Chem. 2023 Jul 24;62(29):11618-11625. Epub 2023 Jul 9. PMID: 37424080.

• Ma Y, Guo W, Mou Q, Shao X, Lyu M, Garcia V, Kong L, Lewis W, Ward C, Yang Z, Pan X, Yi SS, Lu Y. Spatial imaging of glycoRNA in single cells with ARPLA. Nat Biotechnol. 2023 May 22. Epub ahead of print. PMID: 37217750.

• Wu Y, Torabi SF, Lake RJ, Hong S, Yu Z, Wu P, Yang Z, Nelson K, Guo W, Pawel GT, Van Stappen J, Shao X, Mirica LM, Lu Y. Simultaneous Fe2+/Fe3+ imaging shows Fe3+ over Fe2+ enrichment in Alzheimer's disease mouse brain. Sci Adv. 2023 Apr 21;9(16):eade7622. Epub 2023 Apr 19. PMID: 37075105; PMCID: PMC10115418.

• Deng Y, Dwaraknath S, Ouyang WO, Matsumoto CJ, Ouchida S, Lu Y. Engineering an Oxygen-Binding Protein for Photocatalytic CO2 Reductions in Water. Angew Chem Int Ed Engl. 2023 May 8;62(20):e202215719. Epub 2023 Apr 4. PMID: 36916067.

2022 Research

• Pawel GT, Ma Y, Wu Y, Lu Y, Peinetti AS. Binding Affinity Measurements Between DNA Aptamers and their Virus Targets Using ELONA and MST. Bio Protoc. 2022 Nov 5;12(21):e4548. PMID: 36505027; PMCID: PMC9709635.

• Expert Panel on Musculoskeletal Imaging; Stanborough R, Demertzis JL, Wessell DE, Lenchik L, Ahlawat S, Baker JC, Banks J, Caracciolo JT, Garner HW, Hentz C, Lewis VO, Lu Y, Maynard JR, Pierce JL, Scott JA, Sharma A, Beaman FD. ACR Appropriateness Criteria® Malignant or Aggressive Primary Musculoskeletal Tumor- Staging and Surveillance: 2022 Update. J Am Coll Radiol. 2022 Nov;19(11S):S374-S389. PMID: 36436964.

• Zhou Y, Mirts EN, Yook S, Waugh M, Martini R, Jin YS, Lu Y. Reshaping the 2-Pyrone Synthase Active Site for Chemoselective Biosynthesis of Polyketides. Angew Chem Int Ed Engl. 2022 Nov 18. Epub ahead of print. PMID: 36398563.

• Ledray AP, Dwaraknath S, Chakarawet K, Sponholtz MR, Merchen C, Van Stappen C, Rao G, Britt RD, Lu Y. Tryptophan Can Promote Oxygen Reduction to Water in a Biosynthetic Model of Heme Copper Oxidases. Biochemistry. 2022 Oct 10. Epub ahead of print. PMID: 36215733.

• Gramajo ME, Lake RJ, Lu Y, Peinetti AS. In vitro Selection of Aptamers to Differentiate Infectious from Non-Infectious Viruses. J Vis Exp. 2022 Sep 7;(187). PMID: 36155618.

• Song T, Wang X, Yao D, Liang H, Lu Y. Identifying and Differentiating Topological G-Quadruplex Structures with DNA-Encoded Plasmonic Gold Nanoparticles. Angew Chem Int Ed Engl. 2022 Sep 26;61(39):e202204201. Epub 2022 Aug 19. PMID: 35894268; PMCID: PMC9489634.

• Van Stappen C, Deng Y, Liu Y, Heidari H, Wang JX, Zhou Y, Ledray AP, Lu Y. Designing Artificial Metalloenzymes by Tuning of the Environment beyond the Primary Coordination Sphere. Chem Rev. 2022 Jul 27;122(14):11974-12045. Epub 2022 Jul 11. PMID: 35816578.

• Mou Q, Xue X, Ma Y, Banik M, Garcia V, Guo W, Wang J, Song T, Chen LQ, Lu Y. Efficient delivery of a DNA aptamer-based biosensor into plant cells for glucose sensing through thiol-mediated uptake. Sci Adv. 2022 Jul;8(26):eabo0902. Epub 2022 Jun 29. PMID: 35767607; PMCID: PMC9242441.

• Yu Y, Marshall NM, Garner DK, Nilges MJ, Lu Y. Tuning reduction potentials of type 1 copper center in azurin by replacing a histidine ligand with its isostructural analogues. J Inorg Biochem. 2022 Sep;234:111863. Epub 2022 May 20. PMID: 35691263.

• X Wang, G Kim, JL Chu, T Song, Z Yang, W Guo, X Shao, ML Oelze, KC Li and Y Lu. Noninvasive and Spatiotemporal Control of DNAzyme-Based Imaging of Metal Ions In Vivo Using High-Intensity Focused Ultrasound. J. Am. Chem. Soc. 144, 13, 5812–5819. March 18, 2022.

• JJ Zhang, T Lan and Y Lu. Overcoming Major Barriers to Developing Successful Sensors for Practical Applications Using Functional Nucleic Acids. Annu. Rev. Anal. Chem. In press. June 2022.

• Y Wang, NS Reddy Satyavolu, H Yang, Y Lu. Kinetic Reconstruction of DNA-Programed Plasmonic Metal Nanostructures with Predictable Shapes and Optical Properties. J. Am. Chem. Soc. 144, 10, 4410–4421. March 2, 2022.

• N Li, B Zhao, R Stavins, AS Peinetti, N Chauhan, R Bashir, BT Cunningham, WP King, Y Lu, E Valera and X Wang. Overcoming the limitations of COVID-19 diagnostics with nanostructures, nucleic acid engineering, and additive manufacturing. Cur. Opin. Solid State & Material Science, 26, 100966. February 2022.

2021 Research

• N Li, X Wang, J Tibbs, C Che, AS Peinetti, B Zhao, L Liu, P Barya, L Cooper, L Rong, X Wang, Y Lu and BT Cunningham. Label-Free Digital Detection of Intact Virions by Enhanced Scattering Microscopy. J. Am. Chem. Soc. 144, 4, 1498–1502. December 20, 2021.

• Y Gao, S Zhang, C Wu, Q Li, Z Shen,Y Lu and Z-S Wu. Self-Protected DNAzyme Walker with a Circular Bulging DNA Shield for Amplified Imaging of miRNAs in Living Cells and Mice. ACS Nano 15, 19211–19224. December 2, 2021.

• AC Vilbert, Y Liu, H Dai and Y Lu. Recent advances in tuning redox properties of electron transfer centers in metalloenzymes catalyzing oxygen reduction reaction and H₂ oxidation important for fuel cells design. Curr. Opin. Electrochem. 30, 100780. December 2021.

• CE McGhee, Z Yang, W Guo, Y Wu, M Lyu, CJ DeLong, S Hong, Y Ma, MG McInnis, KS O’Shea and Y Lu. DNAzyme-Based Lithium-Selective Imaging Reveals Higher Lithium Accumulation in Bipolar Disorder Patient-Derived Neurons. ACS Cent. Sci. 7, 11, 1809–1820. November 3, 2021.

• CJ Reed, QN Lam, EN Mirts and Y Lu. Molecular understanding of heteronuclear active sites in heme–copper oxidases, nitric oxide reductases, and sulfite reductases through biomimetic modelling. Chem. Soc. Rev. 50, 2486-2539. October 11, 2020.

• AS Peinetti, RJ Lake, W Cong, L Cooper, Y Wu, Y Ma, GT Pawel, ME Toimil-Molares, C Trautmann, L Rong, B Mariñas, O Azzaroni and Y Lu. Direct detection of human adenovirus or SARS-CoV-2 with ability to inform infectivity using DNA aptamer-nanopore sensors. Sci. Adv. 7, eabh2848. September 22, 2021.

• Y Ma, Q Mou, P Yan, Z Yang, Y Xiong, D Yan, C Zhang, Xi Zhu and Y Lu. A highly sensitive and selective fluoride sensor based on a riboswitch-regulated transcription coupled with CRISPR-Cas13a tandem reaction. Chem. Sci. 12, 11740-11747.  August 9, 2021.

• KA Harnden, Y Wang, L Vo, H Zhao and Y Lu. Engineering Artificial Metalloenzymes. In “Protein Engineering: Tools and Applications,” Huimin Zhao, ed. pp177-206. August 6, 2021.

• J Zheng, JL Wai, RJ Lake, S Yee New, Z He and Y Lu. DNAzyme Sensor Uses Chemiluminescence Resonance Energy Transfer for Rapid, Portable, and Ratiometric Detection of Metal Ions. Anal. Chem. 93, 31, 10834–10840. July 26, 2021.

• M Lyu, L Kong, Z Yang, Y Wu, CE McGhee and Y Lu. PNA-Assisted DNAzymes to Cleave Double-Stranded DNA for Genetic Engineering with High Sequence Fidelity. J. Am. Chem. Soc. 143, 9724–9728. June 22, 2021.

• L Yu, A Liu, B Zhang, J Kuang, X Guo, C Tian and Y Lu. Dipolar Coupling-Based Electron Paramagnetic Resonance Method for Protease Enzymatic Characterization and Inhibitor Screening. Chem. Commun. 57, 9602-9605, Issue 75. June 21, 2021.

• S Hong, GT Pawel, R Pei and Y Lu. Recent progress in developing fluorescent probes for imaging cell metabolites. Biomed. Mater. 16, 044108. May 24, 2021.

• EM McConnell, I Cozmaa, Q Mou, JD Brennan, Y Lu and Y Li. Biosensing with DNAzymes. Chem Soc. Rev. 50, 8954-8994. March 7, 2021.

• S Zhang, S Li, R Yan, Z Zhou, Y Wu and Y Lu. Recent advances of using personal glucose meter as a biosensor readout for non-glucose targets. Curr. Anal. Chem. (in press).

• L Que, Jr. and Y Lu. Bio-Coordination Chemistry: An Introduction. Section 8 (Biocoordination Chemistry) Lawrence Que, Jr. and Yi Lu, eds., Comprehensive Coordination Chemistry III, Edwin Constable Gerard Parkin Lawrence Que, eds., pp 1-2. 2021.

• MW Waugh, S Dwaraknath and Y Lu. Advances in Metalloprotein Design and Engineering: Strategies Employed and Insights Gained. In Section 8 (Biocoordination Chemistry) Lawrence Que, Jr. and Yi Lu, eds., Comprehensive Coordination Chemistry III, Edwin Constable Gerard Parkin Lawrence Que, eds. pp 900-928. 2021.

• S Xing, Y Lin, L Cai, PN Basa, AK Shigemoto, C Zheng, F Zhang, SC Burdette and Y Lu. Detection and Quantification of Tightly-Bound Zn²⁺ in Blood Serum Using a Photocaged Chelator and a DNAzyme Fluorescent Sensor. Anal. Chem. 93, 5856–5861. March 31, 2021.

• R-C Qian, Z-R Zhou, W Guo, Y Wu, Z Yang and Y Lu. Cell Surface Engineering using DNAzymes: Metal Ion-mediated Control of Cell-Cell Interactions. J. Am. Chem. Soc. 143, 5737–5744. March 22, 2021.

• W Xu, W He, Z Du, L Zhu, K Huang, Y Lu and Y Luo. Functional Nucleic Acids-Nanomaterials: Development, Properties, and Applications. Angew Chemie Int. Ed. 60, 6890-6918. March 22, 2021.

• S Zhang, Y Luan, M Xiong, J Zhang, R Lake and Y Lu. DNAzyme amplified aptasensing platform for ochratoxin A detection using personal glucose meter. ACS Appl. Mater. Interfaces (Special theme issue on Materials Applications of Aptamers) 13, 9472–9481. February 8, 2021.

• S Tian, R Fan, T Albert, RL Khade, H Dai, KA Harnden, P Hosseinzadeh, J Liu, MJ Nilges, Y Zhang, P Moënne-Loccoz, Y Guo and Y Lu. Stepwise Nitrosylation of the Nonheme Iron Site in an Engineered Azurin and a Molecular Basis for Nitric Oxide Signaling Mediated by Nonheme Iron Proteins. Chem. Sci. 12, 6569-6579. January 19, 2021.

• ID Petrik, R Davydov, M Kahle, B Sandoval, S Dwaraknath, P Adelroth, B Hoffman and Y Lu. An Engineered Glutamate in Biosynthetic Models of Heme-Copper Oxidases Drives Complete Product Selectivity by Tuning the Hydrogen-Bonding Network. Biochemistry 60, 346–355. January 19, 2021.

2020 Research

• Y Wang, MJ Counihan, JW Lin, J Rodríguez-López, H Yang and Y Lu. Quantitative Analysis of DNA-Mediated Formation of Metal Nanocrystals. J. Am. Chem. Soc. 142, 48, 20368–20379. November 18, 2020.

• SG Zambuto, JF Serrano, AC Vilbert, Y Lu, B Harley and S Pedron. Response of neuroglia to hypoxia-induced oxidative stress using enzymatically crosslinked hydrogels. MRS Communications 10, 83-90. September 20, 2020.

• Y Wu, Z Yang and Y Lu. Photocaged functional nucleic acids for spatiotemporal imaging in biology. Curr. Opin. Chem. Biol. 57, 95-104. August 2020.

• S-S Yu, J-J Li, C Cui, S Tian, J-J Chen, H-Q Yu, C Hou, MJ Nilges and Y Lu. Structural Basis for the Quadratic Relationship between Electronic Absorption and Electronic Paramagnetic Resonance Parameters of Type 1 Copper Proteins. Inorg. Chem. 59, 10620–10627. July 20, 2020.

• EN Mirts, SA Dikanov, A Jose, EI Solomon and Y Lu. A Binuclear Cu_A Center Designed in an All α-Helical Protein Scaffold. J. Am. Chem. Soc. 142, 32, 13779–13794. July 14, 2020.

• C Xue, S Zhang, X Yu, S Hu, Y Lu and Z-S Wu. Periodically-Ordered Nick-Hidden DNA Nanowire with Cell-Specific Aptamer Targeting Ligands as Highly Serum-Stable and Selective Theranostic Agents. Angew Chemie Int. Ed. 59, 17540–17547. July 2, 2020.

• JJ Zhang, T Lan and Y Lu. Translating in vitro Diagnostics from Centralized Laboratories to Point-of-Cares using Commercially-Available Handheld Meters. Trac-Trends Anal. Chem. 124, 115782. March 2020.

• M Xiong, Z Yang, RJ Lake, J Li, S Hong, H Fan, X-B Zhang and Y Lu. DNAzyme-Mediated Genetically Encoded Sensors for Ratiometric Imaging of Metal Ions in Living Cells. Angew. Chemie Int. Ed. 132, 1907-1912. January 27, 2020.

• C Ouyang, S Zhang, C Xue, X Yu, H Xu, Z Wang, Y Lu and Z-S Wu. Precision-Guided Missile-Like DNA Nanostructure Containing Warhead and Guidance Control for Aptamer-Based Targeted Drug Delivery into Cancer Cells in Vitro and in Vivo. J. Am. Chem. Soc. 142, 1265-1277. January 2, 2020.

• Y Bai, H Xing, Y Bai, LH Tan, K Hwang, J Li, Y Lu and SC Zimmerman. Independent Control over Size, Valence, and Elemental Composition in the Synthesis of DNA-Nanoparticle Conjugates. Chem. Sci. 11, 1564-1572. January 2, 2020.

• Y Xiong, J Zhang, Z Yang, Q Mou, Y Ma, Y Xiong and Y Lu. DNA Regulated CRISPR-Cas12a Sensors for Point-of-Care Diagnostics of Non-Nucleic Acid Targets. J. Am. Chem. Soc. 142, 207-213. 2020.

• AS Peinetti, R Lake and Y Lu. Functional DNA Sensors for Heavy Metal Ions and Microbial Contaminants in Water. In Water Sensors (Junhong Chen and Matthew Tirrell eds.), World Scientific Publishing Company. In press. 2020.

• S Hong, X Zhang, RJ Lake, GT Pawel, Z Guo, R Pei and Y Lu. A photo-regulated aptamer sensor for spatiotemporally controlled monitoring of ATP in mitochondria of living cells. Chem. Sci. 11, 713-720. 2020.